1. Field of Invention
This invention provides a method, devices and machines to uniformly and simultaneously mix in vessels. The purpose is to provide a robust method, economical devices and very simple machines to uniformly stir the contents of one vessel or thousands of vessels or microplate wells (6 well, 12 well, 24 well, 48 well, 96 well, 384 well, 864 well, 1536 well, 10,000 well and the deep well, "U" bottom, "V" bottom, PCR and other versions of those microplates) at the same time.
2. Description of Prior Art
Suspending particulates in liquids, breaking up aggregates, aeration of gases in liquids, dissolving solids in liquids, emulsifying two liquids or mixing liquids together has usually been accomplished in large vessels, bottles, flasks and test tubes by magnetic horizontal spin stirring, orbital shakers, vortexing, rocking platforms, bubblers or vibrators. In an effort to miniaturize many of the operations that were done in bottles, flasks and test tubes, scientists have shifted to multi well microplates (6, 12, 24, 48, 48 deep well, 96, 96 deep well, 384, 864, 1536 and 10,000 wells/microplate). Microplates are now commonly used in a wide variety of scientific applications to act as mini-reaction vessels for liquid assays. However because of the combination of the small well diameter, the tall height of the column of liquid and the significant attraction of liquid surface tension forces to the walls of small diameter wells (especially in the 48, 96, 384, 864, 1536 and 10,000 well microplates) it is not possible to adequately resuspend particulates, stimulate the growth of microorganisms, break up aggregates, break open cells, aerate gases in to liquids, emulsify two liquids, mix two liquid reagents, or to dissolve a solid in a liquid by simple agitation on an orbital shaker, vortexer, rocker platform, bubbler or by vibration without generating a force so violent that it would throw the liquids out of the miniature vessels. Magnetic horizontal spin stirring has been adapted to 96 well microplates by VARIOMAG-USA. They put spinning permanent magnet stirrers into the wells of a 96 well microplate and place the 96 well microplate on a magnetic stirring system with an individual modulated (driving) electromagnetic stir point engineered under the center of each well. The placement of the wells exactly over a stir point is critical so the spinning stirrers don't hit the well walls and lose synchronization with the driving electromagnetic field, causing them to vibrate in the wells. If they hit the well wall the whole stirrer has to be stopped repositioned and slowly started spinning again. Often when the stir point system is rapidly spinning, the stir magnets in individual wells get out of synchronization with the driving electromagnetic field for no apparent reason or due to the vibration of the stirring action moving the plate. Part of this sensitivity phenomena is due to the physics of the interaction of the magnetic fields of the driving electromagnet and the spinning magnetic stirrer which line up parallel to each other, thus resulting in a weaker magnetic coupling than if the poles were directly opposed to each other. This weak magnetic coupling also is demonstrated if there is a differential viscosity between the liquids of different wells of the same microplate, as this will slow the stirrers in those wells and throw those magnetic stirrers out of sync. The cost of this magnetic stir point system is $2,400.00 for each 96 well plate and the cost of the individual stirring magnets for each well is $2.45 thus bringing the total cost to stir each plate to $2,635.00. Furthermore a unique stir point configuration (6, 12, 24, 48, 96, 384, 1536, and 10000 wells) is required for each well configuration of the microplate well format used. Because of these technical and cost considerations this system has not been widely used. Another way to provide adequate mixing in microplates is by pipetting the contents of each well up and down. This can be done manually or by robotic work stations. There are several robotic work stations that will do this pipet mixing operation but they will just mix 4 to 12 wells at a time and the pipets must be washed or changed between wells. Recently Robbins Scientific introduced the "Hydra" work station which will pipet and mix 96 wells at a time but it costs .about.$30,000 and is still laborious as the pipets must be washed between wells. Furthermore it would be economically impossible to do continuous mixing of multiple microplates simultaneously by pipetting. In addition it would be difficult to place a large robotic workstation in an incubator if microorganisms were the objects being mixed while culturing. Thus the miniaturization of continuous mixing processes on a large number of microplates remains impractical up til now.